Increased Sensitivity of Mitochondrial Respiration to Inhibition by Nitric Oxide in Cardiac Hypertrophy

doi:10.1006/jmcc.2000.1276

Journal of Molecular and Cellular Cardiology

Volume 33, Issue 1, January 2001, Pages 69-82

https://doi.org/10.1006/jmcc.2000.1276 Get rights and content

Abstract

Cardiac hypertrophy is a significant risk factor for the development of congestive heart failure (CHF). Mitochondrial defects are reported in CHF, but no consistent mitochondrial alterations have yet been identified in hypertrophy. In this study selective metabolic inhibitors were used to determine thresholds for respiratory inhibition and to reveal novel mitochondrial defects in hypertrophy. Cardiac hypertrophy was produced in rats by aortic banding. Mitochondria were isolated from left ventricular tissue and the effects of inhibiting respiratory complexes I and IV on mitochondrial oxygen consumption were measured. At 8 weeks post-surgery, 65±2% complex IV inhibition was required to inhibit respiration half maximally in control mitochondria. In contrast, only 52±6% complex IV inhibition was required to inhibit respiration half maximally in mitochondria from hypertrophied hearts (P=0.046). This effect persisted at 22 weeks post-surgery and was accompanied by a significant upregulation of inducible nitric oxide synthase (iNOS, 3.0±0.7-fold,P =0.006). We conclude that respiration is more sensitive to complex IV inhibition in hypertrophy. Nitric oxide is a well documented inhibitor of complex IV, and thus the combination of increased NO^.from iNOS and an increased sensitivity to inhibition of one of its targets could result in a bioenergetic defect in hypertrophy that may be a harbinger of CHF.

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^☆: Please address all correspondence to: Peter G. Anderson, DVM PhD, Department of Pathology, University of Alabama at Birmingham, Volker Hall Rm. G046A, 1670 University Boulevard, Birmingham, AL 35294-0019. Tel: 205 934 2414. Fax: 205 934 1775. E-mail: [email protected]

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Regular ArticleIncreased Sensitivity of Mitochondrial Respiration to Inhibition by Nitric Oxide in Cardiac Hypertrophy☆

Abstract

J Am Coll Cardiol

Ann Thorac Surg

J Surg Res

Cardiol Clin

Exp Mol Path

J Mol Cell Cardiol

FEBS Lett

J Mol Cell Cardiol

J Biol Chem

J Biol Chem

J Biol Chem

J Biol Chem

J Biol Chem

J Mol Cell Cardiol

J Biol Chem

Neurosci Lett

Biochim Biophys Acta

J Biol Chem

J Biol Chem

Arch Biochem Biophys

Free Rad Biol Med

Cardiomyopathy of overload. A major determinant of prognosis in congestive heart failure

New Eng J Med

The prognostic role of left ventricular hypertrophy in patients with or without coronary artery disease

Ann Int Med

Is cardiac failure a consequence of decreased energy reserve?

Circulation

Increased ischemic injury but decreased hypoxic injury in hypertrophied rat hearts

Circ Res

Preischemic glycogen reduction or glycolytic inhibition improves postischemic recovery of hypertrophied rat hearts

Am J Physiol

Regular Article
Increased Sensitivity of Mitochondrial Respiration to Inhibition by Nitric Oxide in Cardiac Hypertrophy☆